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Therapeutic efficacy of fixed dose artesunate-mefloquine for the treatment of acute, uncomplicated Plasmodium falciparum malaria in Kampong Speu, Cambodia.

Leang R, Ros S, Duong S, Navaratnam V, Lim P, Ariey F, Kiechel JR, Ménard D, Taylor WR - Malar. J. (2013)

Bottom Line: The day 0 MQ IC₅₀s ranged from 11.5-238.9 (median 58.6) nM.This TES demonstrated reasonable efficacy in an area of possible reduced artemisinin sensitivity and high MQ IC₅₀s.Efficacy testing of FDC ASMQ should continue in Cambodia and be considered for reintroduction if efficacy returns.

View Article: PubMed Central - HTML - PubMed

Affiliation: National Centre for Parasitology, Entomology and Malaria Control, #372, Monivong Blvd, Corner St, 322, Phnom Penh, Cambodia. rithealeang@gmail.com.

ABSTRACT

Background: Cambodia stopped using co-blistered, non-fixed, artesunate-mefloquine (ASMQ) in 2008 when treatment failure rates approximated 20%. Fixed dose combination (FDC) ASMQ is efficacious against acute uncomplicated, drug resistant Plasmodium falciparum malaria in Southeast Asia but has not been tested in Cambodia.

Methods: A 42-day WHO therapeutic efficacy study (TES) was conducted in 2010 in Oral, Kampong Speu province, south-west Cambodia, in patients with acute uncomplicated P. falciparum. Daily administered FDC ASMQ for three days was dosed by age. Genotyping of isolates at day 0 and day of recrudescence by polymerase chain reaction (PCR) classified post-treatment recurrent falciparum parasitaemia. Ex vivo drug sensitivity testing ([3H] hypoxanthine method) was performed on baseline parasites and reported as the drug concentration inhibiting 50% parasite growth vs no drug (IC₅₀).

Results: Recruited patients numbered 45; five aged <15 years. On day 3, five of 45 [11.1 (3.7-24.05)] % patients were still parasite-positive; one of whom later failed treatment on day 21. There were 5/45 (11.1%) late treatment failures on day 21, 28 and 35; all were PCR diagnosed recrudescent infections. The day 0 MQ IC₅₀s ranged from 11.5-238.9 (median 58.6) nM.

Conclusions: This TES demonstrated reasonable efficacy in an area of possible reduced artemisinin sensitivity and high MQ IC₅₀s. Efficacy testing of FDC ASMQ should continue in Cambodia and be considered for reintroduction if efficacy returns.

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Location of the study sites, Oral, Kampong Speu province, Cambodia.
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Figure 1: Location of the study sites, Oral, Kampong Speu province, Cambodia.

Mentions: This standard WHO TES[16] was conducted in Oral Health Centre in Oral district, Kampong Speu province, about 100 km south-west of Phnom Penh (Figure 1). Malaria is seasonal with an approximate Plasmodium falciparum: Plasmodium vivax ratio of 2:1. The high transmission season is from June to November[17]. The study took place from September 2010 to January 2011. In vitro data (P Lim, unpublished observations but aggregated in reference[10]) from this area in 2001 (n = 13 isolates) and 2003 (n = 54) show median (interquartile ranges, [full ranges]) IC50s for MQ of 17.3 nM (14.6-36.1) [11.9-69.9] and 8.4 nM (3.6-27.5) [1–143.4], respectively.


Therapeutic efficacy of fixed dose artesunate-mefloquine for the treatment of acute, uncomplicated Plasmodium falciparum malaria in Kampong Speu, Cambodia.

Leang R, Ros S, Duong S, Navaratnam V, Lim P, Ariey F, Kiechel JR, Ménard D, Taylor WR - Malar. J. (2013)

Location of the study sites, Oral, Kampong Speu province, Cambodia.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3852322&req=5

Figure 1: Location of the study sites, Oral, Kampong Speu province, Cambodia.
Mentions: This standard WHO TES[16] was conducted in Oral Health Centre in Oral district, Kampong Speu province, about 100 km south-west of Phnom Penh (Figure 1). Malaria is seasonal with an approximate Plasmodium falciparum: Plasmodium vivax ratio of 2:1. The high transmission season is from June to November[17]. The study took place from September 2010 to January 2011. In vitro data (P Lim, unpublished observations but aggregated in reference[10]) from this area in 2001 (n = 13 isolates) and 2003 (n = 54) show median (interquartile ranges, [full ranges]) IC50s for MQ of 17.3 nM (14.6-36.1) [11.9-69.9] and 8.4 nM (3.6-27.5) [1–143.4], respectively.

Bottom Line: The day 0 MQ IC₅₀s ranged from 11.5-238.9 (median 58.6) nM.This TES demonstrated reasonable efficacy in an area of possible reduced artemisinin sensitivity and high MQ IC₅₀s.Efficacy testing of FDC ASMQ should continue in Cambodia and be considered for reintroduction if efficacy returns.

View Article: PubMed Central - HTML - PubMed

Affiliation: National Centre for Parasitology, Entomology and Malaria Control, #372, Monivong Blvd, Corner St, 322, Phnom Penh, Cambodia. rithealeang@gmail.com.

ABSTRACT

Background: Cambodia stopped using co-blistered, non-fixed, artesunate-mefloquine (ASMQ) in 2008 when treatment failure rates approximated 20%. Fixed dose combination (FDC) ASMQ is efficacious against acute uncomplicated, drug resistant Plasmodium falciparum malaria in Southeast Asia but has not been tested in Cambodia.

Methods: A 42-day WHO therapeutic efficacy study (TES) was conducted in 2010 in Oral, Kampong Speu province, south-west Cambodia, in patients with acute uncomplicated P. falciparum. Daily administered FDC ASMQ for three days was dosed by age. Genotyping of isolates at day 0 and day of recrudescence by polymerase chain reaction (PCR) classified post-treatment recurrent falciparum parasitaemia. Ex vivo drug sensitivity testing ([3H] hypoxanthine method) was performed on baseline parasites and reported as the drug concentration inhibiting 50% parasite growth vs no drug (IC₅₀).

Results: Recruited patients numbered 45; five aged <15 years. On day 3, five of 45 [11.1 (3.7-24.05)] % patients were still parasite-positive; one of whom later failed treatment on day 21. There were 5/45 (11.1%) late treatment failures on day 21, 28 and 35; all were PCR diagnosed recrudescent infections. The day 0 MQ IC₅₀s ranged from 11.5-238.9 (median 58.6) nM.

Conclusions: This TES demonstrated reasonable efficacy in an area of possible reduced artemisinin sensitivity and high MQ IC₅₀s. Efficacy testing of FDC ASMQ should continue in Cambodia and be considered for reintroduction if efficacy returns.

Show MeSH
Related in: MedlinePlus